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J Z Nowak

Publications and source records attributed to J Z Nowak.

At least 19 recordsLinked to original sources
PubMed2003

L-745,870 suppresses the nighttime serotonin N-acetyltransferase activity in chick retina: in vivo evidence for agonist activity at D4-dopamine receptors.

This study examined the in vivo activity of L-745,870 at dopamine (DA) D(4) receptors, using the chick retina as a model system. In dark-adapted retinas of various vertebrates, including hen, DA acting via D(4) receptors suppresses melatonin content and activity of serotonin N-acetyltransferase (AA-NAT, a key regulatory enzyme in melatonin synthesis). Systemic administration to chicks of quinpirole (0.1 mg/kg), a high affinity agonist of D(3)/D(4)-DA receptors, potently decreased the nighttime AA-NAT activity of the retina. The quinpirole-evoked decline in the enzyme activity was attenuated by L-745,870 (0.1-10 nmol/eye). In addition to this action, L-745,870 given to chicks either directly into the eye (0.03-10 nmol/eye) or intraperitoneally (0.5-5 mg/kg) decreased the nighttime AA-NAT activity of the retina in a dose-dependent manner. The suppressive effect of L-745,870 on retinal AA-NAT activity was blocked by 2-chloro-11-(4-methylpiperazino)dibenz[ b, f]oxepin, an antagonist of D(4)-DA receptors, but was not affected by raclopride, an antagonist of D(2)/D(3)-DA receptors. Altogether these results indicate that in chicks L-745,870, the potent putative D(4)-DA receptor antagonist, behaves in vivo as a partial D(4) agonist.

Animals↗
PubMed2001

Vasoactive intestinal peptide-stimulated adenosine 3',5'-cyclic monophosphate formation in cerebral cortex and hypothalamus of chick and rat: comparison of the chicken and mammalian peptide.

Chicken and mammalian (human/porcine/rat) vasoactive intestinal peptides (VIP; 0.01-3 microM), whose structures differ by four amino acid residues in 11, 13, 26 and 28 positions, were compared with respect to their ability to stimulate adenosine 3',5'-cyclic monophosphate (cyclic AMP) formation in the hypothalamus and cerebral cortex of chick and rat. In four tested biological systems, the chicken VIP appeared to be significantly more potent in evoking cyclic AMP response than its mammalian counterpart, the differences were more pronounced in the chick tissues, particularly in the hypothalamus, where the mammalian peptide produced only weak (but significant) effect at the highest used dose, i.e. 3 microM. Pituitary adenylate cyclase-activating polypeptide, a VIP-like peptide, applied as a reference drug at 0.1 microM, strongly stimulated cyclic AMP formation in all tested systems. The data demonstrate significant quantitative differences in biological activity between mammalian and non-mammalian peptides tested in brain tissue of chicks and rats, indicating that usage of the mammalian VIP in at least 'avian' studies may lead to some false conclusions.

Adenine↗
PubMed2000

Near-ultraviolet radiation suppresses melatonin synthesis in the chicken retina: a role of dopamine.

Effects of near-ultraviolet radiation (UV-A; 325-390 nm, peak at 365 nm) on melatonin content and activity of serotonin N-acetyltransferase (AA-NAT; a key regulatory enzyme in melatonin biosynthesis) were examined in the retina of chickens. Acute exposure of dark-adapted animals to UV-A light produced a marked decline in melatonin content and AA-NAT activity of the retina. The magnitude of the observed changes was dependent upon duration of the light pulse and age of chickens, with 1-2-week old birds being more sensitive to UV-A action than 6-7-week old ones. The decrease in the nocturnal AA-NAT activity evoked by a 5-min UV-A pulse gradually deepened during the first 30 min after the return of chickens to constant darkness, then the enzyme activity began to rise, reaching nearly complete restoration within 2.5 hr. Systemic administration to chickens of alpha-methyl-p-tyrosine (an inhibitor of catecholamine synthesis; 0.3 g/kg) blocked the suppressive effect of UV-A light on retinal AA-NAT activity. Haloperidol, sulpiride (blockers of D2-family of dopamine (DA) receptors) and 2-chloro-11-(4-methylpiperazino)dibenz[b,f]oxepin (an antagonist of D4-DA receptors), given intraocularly (1-100 nmol/eye) prevented the UV-A light-evoked decrease in AA-NAT activity in the chicken retina in a dose-dependent manner, while raclopride (300 nmol/eye), an antagonist of D2/D3-DA receptors, was ineffective. In dark-adapted chickens exposure to UV-A light increased the DA content of the retina. It is concluded that UV-A radiation, similar to visible light, potently suppresses melatonin biosynthesis in the retina of chicken, with a D4-dopaminergic signal playing the role of an intermediate in this action.

Animals↗
PubMed2000

Effects of cycloheximide and aminophylline on 5-methoxytryptophol and melatonin contents in the chick pineal gland.

The chick pineal gland rhythmically synthesizes two 5-methoxyindoles, melatonin and 5-methoxytryptophol. These rhythms are circadian in nature and have opposite phases. The aim of this study was to determine the effects of cycloheximide, a protein synthesis inhibitor, and aminophylline, an inhibitor of phosphodiesterase, on 5-methoxytryptophol content in the chick pineal gland and to compare this with the drugs' action on pineal melatonin production. Inhibition of melatonin biosynthesis by cycloheximide (1 mg/kg, i.p. ), revealed by a marked reduction in the nighttime activity of serotonin N-acetyltransferase (AA-NAT; a key regulatory enzyme in melatonin synthesis) and melatonin concentrations, was accompanied by a significant increase in 5-methoxytryptophol content. In contrast, administration of aminophylline (100 mg/kg, i.p.) to light-exposed chicks significantly increased pineal AA-NAT activity and melatonin levels and decreased 5-methoxytryptophol concentrations. It is concluded that in the chick the production of pineal 5-methoxytryptophol and melatonin is inversely correlated.

Acetylserotonin O-Methyltransferase↗
PubMed2000

Phase-shifting effects of light on the circadian rhythms of 5-methoxytryptophol and melatonin in the chick pineal gland.

In the chick pineal gland, 5-methoxytryptophol and melatonin concentrations fluctuate in a rhythmic manner. These rhythms are circadian in nature persisting in constant darkness and have opposite phases. Acute exposure of chicks to white light (30 lux for 5, 10, 20, and 30 min) at night increased the amount of pineal 5-methoxytryptophol and decreased pineal melatonin content. A 6 hr pulse of light (100 lux) applied early in the subjective night (CT12-CT18) caused a delay in the phase of the circadian rhythms of 5-methoxytryptophol and melatonin by 3.7 and 4.5 h, respectively, compared to untreated controls. When the 6 hr light pulse was given during the late subjective night (C18 CT24) it advanced the phase of the 5-methoxytryptophol and melatonin rhythms by 8.1 and 11.9 h, respectively. In the chick pineal the phase-advancing effects of light on the circadian rhythms of 5-methoxytryptophol and melatonin were more pronounced than the phase-delaying effects. Our results provide the first evidence that light is capable of phase shifting the 5-methoxytryptophol rhythm in a manner similar to its action on the melatonin rhythm.

Animals↗
PubMed2000

Effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on cyclic AMP formation in the duck and goose brain.

Two molecular forms of pituitary adenylate cyclase-activating polypeptide (PACAP), i.e., PACAP27 and PACAP38 (0.0001-1 microM), as well as vasoactive intestinal polypeptide (VIP; 0.1-3 microM), have been studied for their effects on cyclic AMP formation in the hypothalamus and cerebral cortex of duck and goose. All three peptides concentration-dependently stimulated cyclic AMP production in the tested brain regions of 2-3-weeks-old (young) ducks, with VIP showing at least one order of magnitude weaker activity than PACAP. This characteristics suggests the existence in the duck's brain of adenylyl cyclase-linked PAC1 receptors. Both forms of PACAP also stimulated the nucleotide formation in the cerebral cortex and hypothalamus of 5-6-months-old (adult) ducks or geese grown under natural environment. The peptides-evoked effects in adult and young ducks were comparable, and clearly greater than those found in adult geese. The present data extend our recent observations made on chicks, and suggest PACAP to be a potent stimulator of the cyclic AMP generation in the avian central nervous system.

Age Factors↗
PubMed1999

PACAP-induced formation of cyclic AMP in the chicken brain: regional variations and the effect of melatonin.

We have studied the effects of pituitary adenylate cyclase-activating polypeptide (PACAP27 and PACAP38) on cyclic AMP formation in chick brain, and the action of melatonin upon the PACAP-evoked effects. PACAP stimulated cyclic AMP production in the hypothalamus>cerebral cortex>pineal gland>optic lobes. In the hypothalamus and cerebral cortex, the rank-order of both PACAP forms and VIP in evoking the cyclic AMP response was: PACAP38 approximately PACAP27>>VIP, suggesting the presence in the tested tissues of PAC1 receptors. Melatonin suppressed (IC50=19.8 nM) the PACAP27 (0.1 microM)-induced cyclic AMP response in the hypothalamus, but not in the cerebral cortex. Melatonin also suppressed the hypothalamal cyclic AMP synthesis stimulated by forskolin, but not that evoked by histamine or isoprenaline. Our observations show that PACAP is capable of potently stimulating cyclic AMP formation in some regions of the chick brain, and suggest that the hypothalamus may be a site for a functional interaction between PACAP and the pineal hormone melatonin.

Animals↗
PubMed1999

The effects of near-ultraviolet light on serotonin N-acetyltransferase activity in the chick pineal gland.

Effects of near-ultraviolet light (UV-A; 325-390 nm, peak at 365 nm) on the activity of the pineal serotonin N-acetyltransferase (NAT; a key regulatory enzyme in melatonin biosynthesis) were examined in chicks. Acute exposure of dark-adapted animals to UV-A radiation produced a marked decline in NAT activity of the pineal gland. The magnitude of this suppression was dependent upon duration of the light pulse and the age of the animals. The decrease in the nighttime NAT activity evoked by a 5 min pulse of UV-A light applied during the fourth hour of the dark phase of the 12 hr light:12 hr dark cycle (LD) gradually deepened during the first 40 min after the return of animals to constant darkness, then the enzyme activity began to rise, reaching control values by 2 hr. Exposure of chicks to a 5 min pulse of UV-A light during the ninth hour of the dark phase produced a marked decline in pineal NAT activity, which was reversible after 15 min of darkness. Pretreatment of animals with an inhibitor of catecholamine synthesis, alpha-methyl-p-tyrosine (300 mg/kg, i.p.), or with a blocker of alpha2-adrenergic receptors, yohimbine (2 mg/kg, i.p.), antagonized the suppressive effect of UV-A light on nighttime NAT activity of the chick pineal gland. It is concluded that UV-A irradiation, similar to visible light, potently suppresses melatonin biosynthesis in the chick pineal gland, with an alpha2-noradrenergic signal playing the role of an intermediate in this action.

Animals↗
PubMed1999

[Adenylyl cyclase--isoforms, regulation and function].

Since its discovery in 1956, cyclic AMP (cAMP) has been shown to be a ubiquitous second messenger. It functions as one of many signaling molecules enabling cells to respond to external signals. cAMP is synthesized by adenylyl cyclases (ACs), enzymes that convert adenosine triphosphate (ATP) to cAMP. Three classes of ACs have been cloned based on the conservation of their catalytic domains; they include: class I-ACs from Enterobacteria, including Escherichia coli; class II-"toxic" ACs, including calmodulin-activated enzymes from Bordetella pertussis and Bacillus anthracis; class III-ACs homologues from bacteria to human; they include nine isoformes found in mammals, and designated AC-1 to AC-9. Although ACs can exist in particulate and soluble forms, the former form predominates-at least in mammals. Nine (AC-1-AC-9) mammalian enzymes are stimulated by an "alpha" subunit of Gs-protein (Gs alpha) and by the diterpene forskolin, albeit to varying degrees (with AC-9 being least sensitive to forskolin). In addition to their core signaling capability in response to signals from Gs alpha, the different ACs are capable of receiving signals from a variety of sources, including other G-protein subunits, such as Gi alpha (inhibitory) or G beta gamma (stimulatory or inhibitory, depending on the enzyme), protein kinases (protein kinase A, PKA; protein kinase C, PKC; and calmodulin kinase, Ca(2+)-CaM), and Ca2+ by itself. The effects of activators are often highly synergistic or conditional, suggesting function of ACs as coincidence detectors. The plethora of G-protein-coupled receptors, together with functional differentiation among G-protein subunits and many AC isoforms, permits assembly of a very complex signaling systems with a wide variety of integrative characteristics. This survey presents basic facts on ACs classification and characteristics, and gives a brief review of the recent developments in this important and rapidly growing field of cyclic AMP research.

Adenosine Triphosphate↗
PubMed1999

[Cascade of biochemical events triggered by stimulation of adrenergic receptors in the rat pineal gland--from cell membrane to nucleus].

Pineal glands of various vertebrate species synthesize melatonin in a circadian rhythm generated by an endogenous pacemaker. The levels of melatonin and activity of serotonin N-acetyltransferase (AA-NAT: a penultimate and key regulatory enzyme in melatonin biosynthesis) are low during the light phase and high during the dark phase of any natural or imposed light-dark illumination cycle. The expression of AA-NAT gene in rat pineal gland is regulated by a photoneural system that acts through the adrenergic-cAMP-related mechanisms in pinealocytes. Concomitant stimulation by noradrenaline of beta 1- and alpha 1-adrenergic receptors, in a mechanism of "AND gate" activation, results in a large, 60-100-fold increase in intrapinealocyte cAMP level. The role of cAMP-dependent transcription factors CREB, ICER and Fra-2 in turning on and off the AA-NAT gene expression is discussed.

Animals↗
PubMed1999

[Molecular mechanisms of the biological clock].

Considerable progress has been made in elucidating the mechanisms underlying the generation of circadian rhythmicity. This review describes recent observations and hypothesis on the nature of circadian biological clock in different organisms, such as cyanobacteria (Synechococcus; in which the first noneukaryotic clock was described), Neurospora and Drosophila (representing respectively a fungal and insect system of crucial value for the molecular dissection of circadian timing systems), as well as mammals. Being specific for particular group of organisms, a common model of the circadian biological clock can be depicted which involves a negative transcription/translation-based feedback loop, containing positive and negative elements, and clock genes, as well as clock controlled genes that are directly related to rhythmic metabolism and behavior.

Animals↗
PubMed1999

[Melatonin and its role the circadian function].

Melatonin is a principal hormone of the vertebrate pineal gland. Its production, being under control of a circadian oscillator, follows circadian rhythmicity with high values at night and low values during day-hours. As the nocturnal production of melatonin is proportional to the length of the night (or dark phase of an imposed light-dark illumination cycle), the hormone conveys an important chronobiological message to the whole body, playing the role of a biochemical clock and calendar. This article surveys a current knowledge on regulation of melatonin biosynthesis, receptors and function, and particularly provides a comprehensive view of the role the hormone may play in the vertebrate circadian system.

Animals↗
PubMed1998

5-Methoxytryptophol rhythms in the chick pineal gland: effect of environmental lighting conditions.

5-Methoxytryptophol (5-ML) rhythms were studied in the pineal glands of chicks which were adapted to three different lighting conditions: 12 h light: 12 h dark (LD), constant darkness (DD) and continuous light (LL). Pineal glands of chicks kept under LD conditions exhibited rhythmic fluctuations in 5-ML content. 5-ML levels were low (18+/-2 pg/pineal) during the dark phase of the cycle, they increased approximately 9-fold at the end of the dark phase, and remained high (176 +/-6 pg/pineal) throughout the light period. This pattern of 5-ML content also persisted under conditions of DD, indicating that the 5-ML rhythm is circadian in nature. This is the first evidence of circadian rhythmicity of 5-ML. Pineal 5-ML levels in chicks kept under LL were high (168+/-8 pg/pineal), but did not fluctuate in a rhythmic fashion. Under LD and DD, but not LL, the rhythm of 5-ML in the chick pineal is 180 degrees out of phase with the rhythm of melatonin biosynthesis, an observation suggesting that, at least in this species, the pineal production of these two hormones may be inversely correlated.

Animals↗
PubMed1998

Effects of near-ultraviolet light on the nocturnal serotonin N-acetyltransferase activity of rat pineal gland.

Effects of near-ultraviolet (UV-A; 325-390 nm, peak at 365 nm) light on the activity of the pineal serotonin N-acetyltransferase (NAT; a penultimate and key regulatory enzyme in melatonin biosynthesis) were examined in rats. Acute exposure of dark-adapted animals to UV-A radiation produced a marked suppression of NAT activity of the pineal gland, the effect being dependent on exposure time. The decrease in the night-time NAT activity evoked by a 1-min pulse of UV-A light (as well as by a 15-s pulse of broad-band visible light) gradually deepened during the first 40 min of treatment of animals with constant darkness, then the enzyme activity began to rise reaching control values by 3 h. Treatment of rats with a protein synthesis inhibitor, cycloheximide, attenuated this night-driven reactivation of the pineal NAT activity. The presented results provide evidence that UV-A light is a powerful signal capable of controlling melatonin biosynthesis in rat pineal gland.

Animals↗
PubMed1998

Melatonin and its physiological and therapeutic properties.

Melatonin is a hormone produced mainly by the pineal gland in most vertebrate species, including humans. Recent metabolic, receptor and functional studies created a picture of the melatoninergic system(s) in living organisms, its organization, physiology and a role in some pathologic conditions. The melatonin-generating system is characterized by three basic features: (1) photosensitivity, (2) diurnal (or circadian) rhythmicity (with highest levels of melatonin production occurring at night in darkness), and (3) age-related decline in its activity. Cyclic nocturnal increases of melatonin levels are proportional to the length of nights (or dark periods of an imposed light-dark cycle); the hormone thus conveys a photoperiodic message, and functions in an organism as an internal biochemical clock and calendar. Biological actions of melatonin are mediated via specific melatonin receptors, whose distribution in the body is uneven, yet with decisively highest density in the suprachiasmatic nuclei of the hypothalamus, pars tuberalis of the pituitary, and the retina (particularly in birds and lower vertebrates). Such a distribution of melatonin receptors suggests that the principal physiological role of the hormone is related to both chronobiology and modulation of the body hormonal milieu. This review surveys recent developments in the melatonin field, and summarizes current knowledge on the melatoninergic mechanisms, including the therapeutic aspect related to the hormone.

Animals↗
PubMed1998

[The effect of various wave lengths of light and various duration of impulse times on suppression of n-acetyltransferase activity in the rat pineal gland].

PURPOSE: Rat pineal gland synthesizes melatonin in circadian rhythm, with peak values in a dark phase of an imposed light-dark illumination cycle. Light is the most important environmental factor regulating the melatonin-generating system in this gland. Exposure to light causes a dramatic decline of the night-time levels of these melatoninergic parameters. Effect of white and monochromatic lights of various wavelength on the night-time pineal gland serotonin N-acetyltransferase (NAT) activity was examined in rats. MATERIAL AND METHODS: Wistar rats (12 weeks old) were used. All animals were offered ad libitum access to standard food and water, maintained under an ambient temperature of 21 +/- 2 degrees C, 60 +/- 5% humidity, and exposed to 12 hr light: 12 hr dark illumination cycle for a minimum of 10 days before experiments. The day-time light intensity at the surface of the animals' cages was about 150 luxes. Each experiment was performed at least twice. During the fifth hour of the dark phase of the light-dark illumination cycle individually housed rats were exposed to either white or monochromatic light for 15 sec., 1, 5 or 15 min, and then killed by decapitation. Control animals were quickly decapitated under dim red light (2 luxes). Pineal glands were dissected out and frozen on dry ice. Five rats were sacrificed at each time point. Exposure of animals to light took place in 25 x 21 cm white plastic chamber. Light produced by 5 W 14 bulb (Osram) was passed through a cotton filter or narrow band interference filters, filtered with glass, +/- 7 nm half-peak band-width. The spectral wavelength analysis for each interference filter was performed with the aid of Diode-Spectrophotometer, and irradiance of the light of the three used wavelengths was measured with YSI Radiometer. The estimated peak wavelengths (lambda max) of the filters were: 434 nm (blue), 548 nm (green) and 614 nm (red). The NAT activity was determined in supernatants of tissue homogenates by the radioisotopic method of Steinlechner with Nowak's modifications. RESULTS: NAT of rat pineal gland is very sensitive to the inhibition by light and the marked decline of the night-time NAT activity was observed after 15-sec. pulse of either white or green light (by 44%-white light and 37%-green light). Exposure of rats to white, green, and blue lights for 1 min. decreased NAT pineal activity by 56%, 46%, and 21%, respectively, while the 1 min. pulse of red light did not significantly alter the enzyme activity. CONCLUSION: Interestingly, exposure of rats to any tested lights for as long as 15 min. suppressed NAT activity of rat pineal gland to similar extent, reaching 8-9% of the dark control value.

Animals↗